Evaluating the Safety and Efficacy of a Novel Accelerated Partial Breast Irradiation Regimen

Inclusion Criteria: * Ability to provide informed written consent. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3 or a Karnofsky performance score of ≥ 30%. * Willingness to return to Sanford Cancer Center for follow-up. * Radiation therapy is planned as part of routine care. * On histological examination, the tumor must be either ductal carcinoma in-situ (DCIS) or an invasive ductal carcinoma of the breast. * Patients must be ≥ 50 years old. * Presence of unifocal tumor. * Surgical treatment of the breast must have been a lumpectomy. Placement of surgical clips to delineate the lumpectomy bed is highly recommended, though not required. * The final margins of the resected specimen must be histologically free of tumor (≥ 2 mm for invasive adenocarcinoma and ≥ 3 mm for DCIS). Re-excision of surgical margins is permitted. Gross disease must be unifocal with a pathologic invasive tumor size tumor size ≤ 2.0 cm or pathologic DCIS size ≤ 2.5 cm. * Patients with invasive breast cancer are required to have axillary staging consisting of a sentinel lymph node biopsy. The sentinel lymph node(s) must be negative for regionally metastatic disease, both on routine H\&E evaluation and immunohistochemical staining. Axillary staging is not required for patients with DCIS. * Absence of lymphovascular space invasion. * The tumor must be positive for either the presence of the estrogen or progesterone receptor, and either 0 or +1 for the HER-2/neu receptor on immunohistochemical staining. * The target lumpectomy cavity must be clearly delineated and the target lumpectomy cavity to the whole breast reference volume ratio must be ≤ 30% based on the CT-simulation scan. * Life expectancy of 5 years or longer excluding breast cancer diagnosis(co-morbid conditions taken into considerations by the PI) * Women of child-bearing potential must have a negative pregnancy test before their CT simulation, and must agree to use an effective method of birth control during their radiation therapy treatment course. Exclusion Criteria: * Pregnant women, or women of childbearing potential who are unwilling to employ adequate contraception. * Nuclear grade 3 DCIS or Nottingham grade 3 invasive ductal carcinoma. * Invasive lobular carcinoma, any grade. * Male sex. * Any treatment with radiation therapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to study enrollment * Prior breast or thoracic radiation treatment for any reason. * History of prior invasive breast cancer or DCIS. (Patients with a history of LCIS treated by surgery alone are eligible.) * Paget's disease of the nipple. * Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor. * Patients with a collagen vascular disease; specifically, SLE or scleroderma. * Breast implants. (Patients who have had implants removed are eligible.) * Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements. * Women with a known or suspected predisposition to developing breast cancer (i.e., BRCA1/2 mutations, p53 mutation, etc...) * Women who are pregnant, or women of child-bearing potential who refuse to use an effective method of birth control